Identification of miRNAs as the Crosstalk in the Interaction between Neural Stem/Progenitor Cells and Endothelial Cells.

Xin Wang,Bernd Lethaus,Sebastian Gaus,Yuzhen Xu,Gerhard Schmalz,Aneesha Acharya,Xianda Hu,Yihong Ma,Dirk Ziebolz,Rainer Haak,Zhiqiang Su,Simin Li,Anthony Chukwunonso Ogbuehi,Vuk Savkovic,Hanluo Li,Wen-Jun Tu

doi:10.1155/2020/6630659

Abstract

Aim This study is aimed at identifying genetic and epigenetic crosstalk molecules and their target drugs involved in the interaction between neural stem/progenitor cells (NSPCs) and endothelial cells (ECs). Materials and Methods Datasets pertaining to reciprocal mRNA and noncoding RNA changes induced by the interaction between NSPCs and ECs were obtained from the GEO database. Differential expression analysis (DEA) was applied to identify NSPC-induced EC alterations by comparing the expression profiles between monoculture of ECs and ECs grown in EC/NSPC cocultures. DEA was also utilized to identify EC-induced NSPC alterations by comparing the expression profiles between monoculture of NSPCs and NSPCs grown in EC/NSPC cocultures. The DEGs and DEmiRNAs shared by NSPC-induced EC alterations and EC-induced NSPC alterations were then identified. Furthermore, miRNA crosstalk analysis and functional enrichment analysis were performed, and the relationship between DEmiRNAs and small molecular drug targets/environment chemical compounds was investigated. Results One dataset (GSE29759) was included and analyzed in this study. Six genes (i.e., MMP14, TIMP3, LOXL1, CCK, SMAD6, and HSPA2), three miRNAs (i.e., miR-210, miR-230a, and miR-23b), and three pathways (i.e., Akt, ERK1/2, and BMPs) were identified as crosstalk molecules. Six small molecular drugs (i.e., deptropine, fluphenazine, lycorine, quinostatin, resveratrol, and thiamazole) and seven environmental chemical compounds (i.e., folic acid, dexamethasone, choline, doxorubicin, thalidomide, bisphenol A, and titanium dioxide) were identified to be potential target drugs of the identified DEmiRNAs. Conclusion To conclude, three miRNAs (i.e., miR-210, miR-230a, and miR-23b) were identified to be crosstalks linking the interaction between ECs and NSPCs by implicating in both angiogenesis and neurogenesis. These crosstalk molecules might provide a basis for devising novel strategies for fabricating neurovascular models in stem cell tissue engineering.

Highlights

It is well known that the neurovascular unit (NVU) comprises a collection of cells, which can control interactions between neurons and the vasculature
Differential expression analysis (DEA) was applied to identify neural stem/progenitor cells (NSPCs)-induced endothelial cells (ECs) alterations by comparing the expression profiles between monoculture of ECs and ECs grown in EC/NSPC cocultures
DEA was utilized to identify EC-induced NSPC alterations by comparing the expression profiles between monoculture of NSPCs and NSPCs grown in EC/NSPC cocultures

Summary

Introduction

It is well known that the neurovascular unit (NVU) comprises a collection of cells (e.g., endothelial, neural, and glial cells), which can control interactions between neurons and the vasculature. Increasing evidence has shown that the cell contactdependent interactions between neural stem/progenitor cells (NSPCs) and endothelial cells (ECs) can drive the coupling of neurogenesis and angiogenesis. NSPCs can promote morphogenesis and angiogenesis of ECs by expressing angiogenic factors such as vascular endothelial growth factor (VEGF) [4]. VEGF has been demonstrated to promote neurogenesis, neuronal patterning, neuroprotection, and glial growth of NSPCs [5]. ECs can stimulate survival, proliferation, neuronal differentiation, and neurogenesis of NSPCs by secreting neurotrophic factors such as brain-derived neurotrophic factor (BDNF) [6,7,8]. Current evidence indicates that the interactions between NSPCs and ECs are governed by several common crosstalk factors that regulate both the neurogenic and angiogenic processes

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Conclusion